title: Essential role for UVRAG in autophagy and maintenance of cardiac function.
abstract: OBJECTIVE
  Ultraviolet irradiation resistance-associated gene (UVRAG) is a tumour suppressor candidate that regulates cell autophagy and endocytosis. However, the in vivo function of UVRAG remains poorly understood. We sought to determine the physiological role of UVRAG in the heart.
  
  
  RESULTS
  We characterized mice with disruption of the UVRAG gene by piggyBac (PB) transposon insertion. PB construct was inserted into intron 14 of the UVRAG gene and disruption of UVRAG transcript was confirmed by reverse transcript-polymerase chain reaction. Immunoblotting revealed that UVRAG was deficient in multiple tissues. Autophagic flux was attenuated in UVRAG-deficient (UVRAG(PB/PB)) mouse embryonic fibroblasts. In UVRAG-deficient hearts, autophagosomes were accumulated and autophagic flux, assessed as the increased protein abundance of LC3 II in chloroquine-treated animals, was impaired. UVRAG-deficient mice were viable, fertile, and developmentally normal. However, they developed age-related cardiomyopathy associated with compromised cardiac function. In addition, inflammatory response was enhanced in UVRAG-deficient hearts.
  
  
  CONCLUSIONS
  Collectively, our findings suggest that UVRAG is essential for the regulation of autophagy and maintenance of cardiac function.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zongpei
authors.initials: Z
authors.lastname: Song
authors.forename: Lin
authors.initials: L
authors.lastname: An
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001343:Autophagy; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000502:physiology*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D011247:Pregnancy; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D025521:Tumor Suppressor Proteins; C512859:UVRAG protein, mouse
keywords: Autophagosome; Autophagy; Cardiomyopathy; Inflammation; UVRAG